Various foodstuffs, liquids and other degradable material can be sterilely packaged in pouch-type flexible containers made from webs of flexible film that are sealed together along the unconnected peripheral sides. This type of flexible packaging is commonly referred to as form, fill and seal packages. There are a number of advantages to these pouch-type flexible containers, including weight, durability and low cost to produce. To a lesser extent, a few medical solutions have been sterilely packaged in pouch-type flexible containers by form, fill and seal packaging machines.
One disadvantage of these pouch-type flexible containers for medical solution use is that it is difficult to make a sterile connection to the flexible container for drawing the contents in a sterile manner. The wall material of the container is flexible and without any rigidity. Thus, it is difficult to obtain a liquid tight and leakproof connection through the flexible wall using traditional medical connectors such as needles or piercing pins.
Traditionally, it has been necessary for flexible solution containers used for parenteral solutions to include rigid administration ports to facilitate sterile access to the solution. These pre-formed, rigid administration ports are often molded from a suitable medical grade plastic material. The usual considerations for the material used for the administration ports are the ease of molding and the ability to be securely bonded to the flexible film sheets. For example, a "boat" administration port may be sealed by many known thermal bonding processes between the opposed inner layers of two flexible film sheets so as to form a flexible solution container. Ultrasonic welding or solvent bonding may also be used to seal the boat port between the film layers.
The majority of flexible films used for flexible solution containers are monolayer PVC films. Recently, a few multiple-layer, extrusion or adhesive laminated films have been used in form, fill and seal packaging for producing flexible solution containers. The inner, solution contacting layer must be substantially inert to the solution. Also the inner layer of the film must be readily bondable to itself. Furthermore, the inner film layer must be compatible with any material used for attachable components, such as administration ports. The outer layer of the laminated film must be durable and also compatible with other materials that may contact or be attached to the outside surface. If neither the inner or outer layer has the desired solution maintaining and barrier characteristics, such as low moisture and/or oxygen permeability, additional film layers may be required between the inner and outer layers.
A primary disadvantage of known flexible solution containers assembled according to the above described boat port construction is that the port material typically has a higher oxygen permeability than the film material. In the known form, fill and seal flexible solution containers, the permeability characteristic of the port material is much greater than the similar characteristic for the laminated film used to make the flexible container. Thus, the administration port of known flexible solution containers is often the weakest part of the barrier characteristics. This factor becomes extremely important for certain medical solutions which are sensitive to oxygen or other penetrating gases, for example.
In the past, any of the above deficiencies has been overcome by overwrapping the flexible solution container and/or the administration ports, with an overwrap material. While this redundancy in packaging may provide the desired barrier characteristics, the overwrap material introduces two important disadvantages. First, there is the additional cost to fabricate and later dispose of the overwrap. Second, there is concern that extractables from the overwrap material may migrate into the contained solution during post filling procedures, such as during the sterilization process or even during shelf life.
Pre-formed rigid administration ports constitute potential places of leakage and are potential points of entry in an otherwise sealed, durable, flexible container. Moreover, the rigid ports make it more difficult to arrange an outer protective package around the flexible container. Also the protective overwrap only initially prevents the packaged solution from losing its potency due to evaporation or diffusion. When the overwrap is removed or breached, the administration ports positioned between two layers of film is an effective breach in the barrier characteristics of the flexible container for certain sensitive drugs.
For example, due to the sensitivity of certain solutions to oxygen, such as amino acids, it is desirable to use materials that minimize the permeation of oxygen for the flexible solution containers for parenteral administration of these solutions. The properties of the film can be controlled easily by the choice of the film components and structure. However, the oxygen permeation properties of the port system are not as easily controlled. Thus, it is desirable to use the film and its good barrier properties as both the solution contacting surface and the pierceable diaphragm of the administration port system so that the barrier properties of the port system are consistent with the barrier properties of the flexible container. However this consistency is not achieved in known flexible containers having pre-formed rigid port systems sealed between the film layers of the flexible container.
Moreover, the known flexible container and administration port systems often include an entry port in addition to the administration port. The entry ports are likewise inserted between film layers at the perimeter seal. Both ports are thus a breach through an otherwise effective perimeter barrier. A pierceable diaphragm is provided in the administration port to prevent an outflow of solution. During packaging, the flexible container may be filled through the entry port. After filling, the entry port is sealed, but the ports, and specifically the exposed port material, is the potential point of entry for compromising the barrier characteristics.
Flange ports are an alternative to boat ports and may be advantageously sealed to a film surface. However for the flexible solution container produced by the known form, fill and seal process, the use of flange ports does not remove the barrier deficiency. For example, a flexible parenteral solution container including a flange-sealed port assembly is disclosed in U.S. Pat. No. 4,695,337 to Christine and in U.S. Pat. No. 4779397 to Christine et al. A major disadvantage of the disclosed flexible solution container is that the flexible film barrier of the flexible container is purposefully breached during the assembly steps to mount and seal the administration port or fitment to the inside surface of the flexible container, as seen for example in FIGS. 4a-4d of the patents.
Thus, due to the inherent breaches in the film barriers for known flexible solution containers in current use, parenteral solutions may be subjected to degradation during the shelf life of the product solution. While an overwrap may provide some protection for the flexible container and the port administration system from contamination or degradation during shelf life, the overwrap introduces additional concerns that are increasingly desirable to avoid.
Thus, it is desirable to utilize the unbreached and completely intact film of the flexible solution container as the primary barrier for medical solutions packaged in flexible solution containers and especially for certain oxygen or other gas sensitive parenteral solutions.
It is therefore desirable to manufacture a flexible container that provides integral barrier characteristics without any compromises in the barrier characteristics of the film material used for the flexible solution container.
It is also desirable to manufacture a flexible container that includes an attached administration port system that is accessible by a variety of piercing pins, including center point pins, beveled pins and blunt pins as well as a port system that is compatible with the various lengths and other dimensions of the most common piercing pins.
It is also desirable to manufacture a flexible container that allows the maximum amount of solution to be readily, completely and easily delivered in a sterile manner from the container.